This is a 2-yr proposal of research examining the influence of ethanol on the neural mechanisms that control higher cognitive functions, in particular spatial navigation. Spatial navigation is a fundamental behavior that is essential for accurate moving about our environment and for efficiently changing routes to goal locations in the face of environmental changes. Navigation requires a number of higher cognitive functions including perception, attention, planning, judgment, and memory. In humans, acute alcohol intoxication impairs several higher cognitive functions including navigation, memory and attention. Alcohol intoxication is a leading contributor to motor vehicle accidental deaths, sports accidents, impairments in complex behaviors, and ataxia in the United States. Acute alcohol intoxication limits the ability to form new memories, and impairs the ability to effectively use established spatial memories. The brain mechanisms responsible for these effects of alcohol are not known. Understanding the neurobiological mechanisms that are responsible for the detrimental behavioral actions of acute alcohol is essential for developing effective strategies to treat or prevent problems associated with alcohol abuse. The long term goal of this research is to define the brain mechanisms responsible for alcohol's effects on navigation. Previous behavioral studies have shown that acute ethanol disrupts spatial memory in rats and mice. In contrast, acute ethanol has minimal effects on the spatial firing of hippocampal neurons (place cells). Thus, there is a disconnection between the behavioral and electrophysiological influences of ethanol. This discrepancy suggests that ethanol's effect on spatial cognition may result from actions of the drug on brain systems other than the hippocampus. The dose-dependent effects of acute ethanol on hippocampal-dependent and anterior thalamicdependent spatial navigation will be determined in C57BL/6J mice in Aim 1. Aim 2 will determine the dose dependent effects of acute ethanol on hippocampal place cells and anterior thalamic head direction cell responses. This second aim will provide an indication of the consequences of ethanol on the neurobiological correlates of spatial information processing. Aim 3 is designed to examine the simultaneous effect of ethanol on the firing patterns of multiple neurons recorded in parallel from the anterior thalamus and hippocampus of mice engaged in navigation tasks. This innovative research coupling electrophysiological and cognitive measures will provide important data regarding the neural networks that are responsible for ethanol's influence on spatial cognition.